ABSTRACT
Pathogenic New World arenaviruses (NWAs) cause haemorrhagic fevers and can have high mortality rates, as shown in outbreaks in South America. Neutralizing antibodies (Abs) are critical for protection from NWAs. Having shown that the MOPEVAC vaccine, based on a hyperattenuated arenavirus, induces neutralizing Abs against Lassa fever, we hypothesized that expression of NWA glycoproteins in this platform might protect against NWAs. Cynomolgus monkeys immunized with MOPEVACMAC, targeting Machupo virus, prevented the lethality of this virus and induced partially NWA cross-reactive neutralizing Abs. We then developed the pentavalent MOPEVACNEW vaccine, expressing glycoproteins from all pathogenic South American NWAs. Immunization of cynomolgus monkeys with MOPEVACNEW induced neutralizing Abs against five NWAs, strong innate followed by adaptive immune responses as detected by transcriptomics and provided sterile protection against Machupo virus and the genetically distant Guanarito virus. MOPEVACNEW may thus be efficient to protect against existing and potentially emerging NWAs.
Subject(s)
Arenaviruses, New World , Animals , Arenaviruses, New World/metabolism , Vaccines, Combined , Macaca fascicularis/metabolism , Antibodies, Neutralizing , GlycoproteinsABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19). It emerged from China in December 2019 and rapidly spread across the globe, causing a pandemic with unprecedented impacts on public health and economy. Therefore, there is an urgent need for the development of curative treatments and vaccines. In humans, COVID-19 pathogenesis shows a wide range of symptoms, from asymptomatic to severe pneumonia. Identifying animal models of SARS-CoV-2 infection that reflect the clinical symptoms of COVID-19 is of critical importance. Nonhuman primates (NHPss) correspond to relevant models to assess vaccine and antiviral effectiveness. This review discusses the use of NHPs as models for COVID-19 research, with focus on the pathogenesis of SARS-CoV-2 infection, drug discovery and pre-clinical evaluation of vaccine candidates.
